title: Pharmacokinetic analysis of a combined chemoendocrine treatment with paclitaxel and toremifene for metastatic breast cancer.
abstract: BACKGROUND
  Multidrug resistance protein could be a target for improving the efficacy of paclitaxel (PXL). Toremifene (TOR) may moderate P-gp-related drug resistance in vitro. Some P-gp moderators may change the pharmacokinetic parameters of PXL in vivo. A pharmacokinetic (PK) study in metastatic breast cancer patients (MBC) was conducted to determine the safety and efficacy of PXL and TOR.
  
  
  METHODS
  Fifteen patients received 80 mg/m(2) PXL (i.v.) weekly and 120 mg/body TOR (p.o.) daily. For the pharmacokinetic study, PXL was administered on days 1, 8, 15, 32, and 39; TOR was given from day 18 to the end of study. On days 1, 8, 15, 18, 32, and 39, blood samples were collected from the patients who received either PXL alone or PXL + TOR, and these were analyzed by high-performance liquid chromatography.
  
  
  RESULTS
  Among the 15 patients enrolled in the study, one showed a partial response, and eight had a stable disease. TOR caused no specific adverse events that were greater than grade 3, and its toxicity profile in combination with PXL was similar to that of PXL monotherapy. The PK profile of PXL was similar with or without TOR. The PK parameters of PXL indicated no inter- or intra-patient variability in previously treated patients with MBC. No increased PXL toxicity was observed.
  
  
  CONCLUSIONS
  The PK profile of combined PXL and TOR was similar to that of PXL monotherapy. The addition of TOR to PXL in previously treated patients with MBC appears safe.
authors.affiliation: Department of Breast Oncology, Saitama International Medical Center, Saitama Medical University, 1397-1 Yamane, Hidaka, 350-1298, Japan. tsaeki@saitama-med.ac.jp
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Saeki
authors.forename: Atsushi
authors.initials: A
authors.lastname: Okita
authors.forename: Kenjiro
authors.initials: K
authors.lastname: Aogi
authors.forename: Tomokazu
authors.initials: T
authors.lastname: Kakishita
authors.forename: Riki
authors.initials: R
authors.lastname: Okita
authors.forename: Naruto
authors.initials: N
authors.lastname: Taira
authors.forename: Yumi
authors.initials: Y
authors.lastname: Ohama
authors.forename: Shigemitsu
authors.initials: S
authors.lastname: Takashima
authors.forename: Kiyohiro
authors.initials: K
authors.lastname: Nishikawa
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001859:Bone Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000556:secondary; D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D064420:Drug-Related Side Effects and Adverse Reactions; D005260:Female; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000556:secondary; D008175:Lung Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000556:secondary; D008875:Middle Aged; D009367:Neoplasm Staging; D017239:Paclitaxel / Q000008:administration & dosage; D011379:Prognosis; D015996:Survival Rate; D014018:Tissue Distribution; D017312:Toremifene / Q000008:administration & dosage; D016896:Treatment Outcome
chemical_list: D017312:Toremifene; D017239:Paclitaxel